Maybe you need to exclude something from Defender ('rebadged' MSE Ψ)
That said I've never had to exclude anything in anything at anytime.
Calibre server works for me under W10 via edge, firefox and chrome
on the same box. And my W7 laptop can access the same w10 based calibre servers
locally with IE11, firefox and chrome.
I haven't changed anything regarding calibre server since upgrading to W10. IIRC calibre-server has always '
just worked', I run multiple calibre-servers via command files with different port numbers for different libraries.
My use of calibre-server is local area only - ie no requirement for wide area access.
BR